Citation: Yaodong You, Kun Zhu, Jie Wang, Qi Liang, Wen Li, Lin Wang, Baojun Guo, Jing Zhou, Xuanlin Feng, Jianyou Shi. ROCK inhibitor: Focus on recent updates[J]. Chinese Chemical Letters, ;2023, 34(12): 108336. doi: 10.1016/j.cclet.2023.108336 shu

ROCK inhibitor: Focus on recent updates

Yaodong You ^{a, b, 1} ,
Kun Zhu ^{a, 1} ,
Jie Wang ^c ,
Qi Liang ^d ,
Wen Li ^a ,
Lin Wang ^e ,
Baojun Guo ^a ,
Jing Zhou ^a ,
Xuanlin Feng ^{f, *,} ,
Jianyou Shi ^{g, *,}

a.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
b.
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu 610072, China
c.
Guizhou University of Traditional Chinese Medicine, Guiyang 550002, China
d.
College of Medicine, Southwest Jiaotong Unive, Chengdu 610031, China
e.
College of Food and Bioengineering, Xihua University, Chengdu 610039, China
f.
Department of Emergency Intensive Care Unit, Sichuan Academy of Medical Sciences & Sichuan Province People's Hospital, Chengdu 610072, China
g.
Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology, Chengdu 610072, China

23376592@qq.com

shijianyoude@126.com

Received Date: 5 January 2023
Revised Date: 8 March 2023
Accepted Date: 12 March 2023
Available Online: 15 March 2023

Figures(12)

Rho-associated coiled-coil-containing protein kinase (ROCK) belongs to the serine-threonine family, and ROCK is involved in a variety of biological processes including cell migration, adhesion, proliferation and differentiation through phosphorylation of different downstream substrates. The aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases, including cancer, neurological diseases, inflammation, cardiovascular diseases and glaucoma. Therefore, the ROCK inhibitors have potential applicability for treating the aforementioned diseases. Four small molecule ROCK inhibitors have been approved for clinical use: fasudil, ripasudil, netarsudil and belumosudil. In recent years, more small molecule ROCK inhibitors have been identified. This paper reviews the ROCK inhibitors reported in past seven years. We mainly focused on the summarization of the structure–activity relationships, inhibitory efficacy, pharmacological mechanisms and the relevant clinical studies of the reported ROCK inhibitors. Besides the small molecular inhibitors, the peptides and biological extracts which exhibit ROCK inhibitory effects are also included. We also provide suggestions for the future development of the potent ROCK inhibitors.
- ROCK-Ⅰ,
- ROCK-Ⅱ,
- ROCK inhibitor,
- ROCK signaling pathway,
- Structure–activity relationship,
- Pharmacological activity
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